EFFECT OF LOW-DENSITY-LIPOPROTEIN ON ADENOSINE RECEPTOR-MEDIATED CORONARY VASORELAXATION IN-VITRO

We investigated the effect of low density lipoprotein (LDL) on vasorel axations and nitric oxide generation induced by the adenosine analogs, 5'-(N-ethylcarboxamide)adenosine, yl)phenylethyl-amino-5'N-ethylcarbo xamidoadenosine and/or 2-chloroadenosine in porcine coronary artery ri ngs in vitro. Preincubation of tissues with native LDL (100 and 200 mu g/ml) for 4 hr in the absence or presence of copper sulfate (5 mu M) selectively attenuated the endothelium-dependent relaxations elicited by 5'-(N-ethylcarboxamide)adenosine and 2-p-(2-carboxyethyl)phenylethy l-amino-5' ideoadenosine without altering the response to 2-chloroaden osine which produced endothelium-independent relaxation. The 4-hr expo sure of tissues to native LDL (100 mu g/ml) also inhibited the product ion of nitrite induced by 5'-(N-ethylcarboxamide)adenosine in endothel ium-intact rings. These effects were associated with enhanced oxidatio n of the lipoprotein. The inhibitory action of LDL on tissue relaxatio ns and nitrite generation as well as the oxidation of the lipoprotein were all prevented by high density lipoprotein (100 mu g/ml). In contr ast, a relatively short period (20 min) of tissue incubation with nati ve LDL produced no alterations of the relaxations and nitrite producti on evoked by 5'-(N-ethylcarboxamide)adenosine and 2-p-(2-carboxyethyl) phenylethyl-amino-5' N-ethylcarboxamide)adenosine. Under this conditio n, the oxidation of LDL was not also significantly altered. In conclus ion, the results indicate that in coronary artery LDL, with oxidative modification, causes attenuation of nitric oxide-mediated endothelial responses induced by adenosine receptors activation, and this effect i s prevented by high density lipoprotein. Such modulation may be of imp ortance in hypercholesterolemia and in the development of atherosclero sis.